The epithelial–mesenchymal plasticity landscape: principles of design and mechanisms of regulation

Haerinck, Jef; Goossens, Steven; Berx, Geert

doi:10.1038/s41576-023-00601-0

Cited by 38 publications

(22 citation statements)

References 389 publications

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“…This aligns with previous observations delineating a 'mesenchymal signature' as one of the major transcriptional programs present in primary cells from different tissue types, across developmental lineages 34 . Transitioning towards such a mesenchymal signature may transcriptionally prime different precursor lineages to increase their cell fate plasticity, akin to what is observed in various types of metastatic cancers, while still maintaining partially distinct transcription and chromatin memories of their embryonic origins 35,36 . Indeed, skeletogenic cells of the three lineages investigated here all start out as embryonic epithelia and undergo an epithelial-tomesenchymal transition (EMT), before migrating to their respective anatomical locations in the periphery [37][38][39] .…”

Section: Transcriptional Recoding and Lineagememory In Mesenchymal Cellsmentioning

confidence: 94%

Distinct Gene Regulatory Dynamics Drive Skeletogenic Cell Fate Convergence During Vertebrate Embryogenesis

Wang,

Di Pietro-Torres,

Feregrino

et al. 2024

Preprint

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Cell type repertoires have expanded extensively in metazoan animals, with some clade-specific cells being paramount to their evolutionary success. A prime example are the skeletogenic cells of vertebrates that form the basis of their developing endoskeletons. Depending on anatomical location, these cells originate from three different embryonic precursor lineages - the neural crest, the somites, and the lateral plate mesoderm - yet they converge developmentally towards similar cellular phenotypes. Furthermore, these lineages have gained skeletogenic competency at distinct timepoints during vertebrate evolution, thus questioning to what extent different parts of the vertebrate skeleton rely on truly homologous cell types. Here, we investigate how lineage-specific molecular properties of the three precursor pools are integrated at the gene regulatory level, to allow for phenotypic convergence towards a skeletogenic cell fate. Using single-cell transcriptomics and chromatin accessibility profiling along the precursor- to-skeletogenic cell continuum, we examine the gene regulatory dynamics associated with this cell fate convergence. We find that distinct transcription factor profiles are inherited from the three precursor states, and that lineage-specific enhancer elements integrate these different inputs at the cis-regulatory level, to execute a core skeletogenic program. We propose a lineage-specific gene regulatory logic for skeletogenic convergence from three embryonic precursor pools. Early skeletal cells in different body parts thus share only a partial deep homology. This regulatory uncoupling may render them amenable to individualized selection, to help to define distinct morphologies and biomaterial properties in the different parts of the vertebrate skeleton.

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Section: Transcriptional Recoding and Lineagememory In Mesenchymal Cellsmentioning

confidence: 94%

Distinct Gene Regulatory Dynamics Drive Skeletogenic Cell Fate Convergence During Vertebrate Embryogenesis

Wang,

Di Pietro-Torres,

Feregrino

et al. 2024

Preprint

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show abstract

“…At the destined location, these mesenchymal-like cells can regain their epithelial phenotype by undergoing a mesenchymal–epithelial transition (MET) in a binary process. Meanwhile, the existence of cells with a series of intermediate states and hybrid epithelial/mesenchymal phenotypes can be demonstrated ( Orgaz et al, 2014 ; Haerinck et al, 2023 ). Increasing evidences suggest that EMT can contribute to cellular diversity during development and adulthood.…”

Section: Cell Plasticity and Migrationmentioning

confidence: 99%

Plasticity in cell migration modes across development, physiology, and disease

Pourjafar,

Tiwari

2024

Front. Cell Dev. Biol.

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Cell migration is fundamental to both development and adult physiology, including gastrulation, brain development, angiogenesis, wound healing, bone remodeling, tissue homeostasis, and the immune response. Additionally, misguided cellular migration is implicated in disease pathologies such as cancer metastasis and fibrosis. The microenvironment influences cell migration modes such as mesenchymal, amoeboid, lobopodial, and collective, and these are governed through local signaling by affecting the gene expression and epigenetic alteration of migration-related genes. Plasticity in switching between migration modes is essential for key cellular processes across various contexts. Understanding the mechanisms of cell migration modes and its plasticity is essential for unraveling the complexities of this process and revealing its implications in physiological and pathological contexts. This review focuses on different modes of cell migration, including their aberrant migration in disease pathologies and how they can be therapeutically targeted in disease conditions such as cancer.

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“…Instead of EMT, EMPs contribute to tumor progression by promoting therapy resistance and immune cell evasion ( Cook and Vanderhyden, 2022 ). Epithelial-mesenchymal plasticity is characterized by five distinct factors: local microenvironment, lineage specification, cell identity, genome, hysteresis (cell memory), and noise-driven stochastic state transitions ( Cook and Vanderhyden, 2020 ; Haerinck et al, 2023 ).…”

Section: Epithelial-mesenchymal Plasticitymentioning

confidence: 99%

Cancer spreading patterns based on epithelial-mesenchymal plasticity

Wang,

Yan

2024

Front. Cell Dev. Biol.

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Introduction: Metastasis is a major cause of cancer-related deaths, underscoring the necessity to discern the rules and patterns of cancer cell spreading. Epithelial-mesenchymal plasticity contributes to cancer aggressiveness and metastasis. Despite establishing key determinants of cancer aggressiveness and metastatic ability, a comprehensive understanding of the underlying mechanism is unknown. We aimed to propose a classification system for cancer cells based on epithelial-mesenchymal plasticity, focusing on hysteresis of the epithelial-mesenchymal transition and the hybrid epithelial/mesenchymal phenotype.Methods: We extensively reviewed the concept of epithelial-mesenchymal plasticity, specifically considering the hysteresis of the epithelial-mesenchymal transition and the hybrid epithelial/mesenchymal phenotype.Results: In this review and hypothesis article, based on epithelial-mesenchymal plasticity, especially the hysteresis of epithelial-mesenchymal transition and the hybrid epithelial/mesenchymal phenotype, we proposed a classification of cancer cells, indicating that cancer cells with epithelial-mesenchymal plasticity potential could be classified into four types: irreversible hysteresis, weak hysteresis, strong hysteresis, and hybrid epithelial/mesenchymal phenotype. These four types of cancer cells had varied biology, spreading features, and prognoses.Discussion: Our results highlight that the proposed classification system offers insights into the diverse behaviors of cancer cells, providing implications for cancer aggressiveness and metastasis.

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The epithelial–mesenchymal plasticity landscape: principles of design and mechanisms of regulation

Cited by 38 publications

References 389 publications

Distinct Gene Regulatory Dynamics Drive Skeletogenic Cell Fate Convergence During Vertebrate Embryogenesis

Distinct Gene Regulatory Dynamics Drive Skeletogenic Cell Fate Convergence During Vertebrate Embryogenesis

Plasticity in cell migration modes across development, physiology, and disease

Cancer spreading patterns based on epithelial-mesenchymal plasticity

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